You are here

January 27, 2015, PNLR E-newsletter

New clinical trial rules would expand adverse event disclosures

Alyssa E. Lambert

The U.S. Department of Health and Human Services (HHS) has issued a notice of proposed rulemaking that would require manufacturers and researchers to publicly disclose more information about clinical drug and device trials, especially concerning adverse events. A recent report published in the New England Journal of Medicine (NEJM) highlighted key aspects of the proposed rulemaking. The public comment period closes on Feb. 19.

Many clinical trial results for drugs and devices are not published, leaving a void in the publicly available data—a problem that has plagued the medical community and consumers alike. Part of this problem was remedied when Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) was passed, which requires certain clinical drug and device trials in the United States to be registered with the publicly accessible ClinicalTrials.gov. The FDAAA also requires summary results of those trials to be submitted to the website.

The new proposed rules would clarify and heighten some of the FDAAA’s requirements for clinical trial information and registration. The amount and depth of adverse event information would be significantly expanded. Under current law, manufacturers and researchers have to provide only two tables on adverse events: one including serious adverse events and another listing adverse events that occurred in at least 5 percent of the study group. The new rules would require disclosure of additional data, including the time frame during which the adverse event data was collected, the approach used to collect the data, and a table listing deaths from any cause.

HHS also proposed several other changes. The responsible party—for example, the manufacturer—would have to register an applicable clinical trial within 21 days after enrolling the first participant and report certain data at the time of registration, including a description of the trial, participant recruitment information, and location and contact information. Also, summary results from clinical trials must be submitted to ClinicalTrials.gov regardless of whether the FDA has approved the drug or device. Currently, results have to be submitted only for products the agency approves, licenses, or clears for marketing. Data submitted to the website must be updated—if there are changes—at least annually, and timely correction of errors is required.

According to the NEJM report, which was published on Dec. 24, HHS is proposing the new rules “to reduce bias in publicly available information about investigational products stemming from selective disclosure of results” and “to assist those attempting to assess the benefits and harms of entire classes of drugs or devices,” among other reasons. The report also analyzes the proposed rulemaking. For example, the time frame disclosure requirement for adverse events, which does not exist under current rules, could “assist in comparing the relative frequency of adverse events across trials.” Disclosing mortality rates in clinical trials “would make it possible to determine the total number of deaths during a trial per study group.” Now, deaths can be reported as merely adverse events without mentioning that the participant died, or they may not be reported at all.

Problems with clinical trial data for drugs and devices have spilled over into courtrooms. For example, as part of litigation over the blood thinner Pradaxa, independent medical experts called into question RE-LY, the clinical trials that led to Pradaxa’s approval. The experts wanted an investigation into RE-LY’s accuracy: The results were amended several times after initially omitting key adverse event findings. In May, more than 4,500 consumers harmed by Pradaxa received a $650 million settlement.

Bryan Aylstock, who handles drug and device cases, said the rules are “a significant step in the right direction,” and the new adverse event disclosures are crucial. “By requiring this data to be disclosed, researchers can look for trends and significant associations across the studies to find rare, but serious, side effects related to pharmaceutical drugs,” said Aylstock, of Pensacola, Fla. “Historically, clinical trials that were not helpful to the products at issue have been ‘buried’ and never see the light of day. These rules will help avoid that happening in the future.”

Seth Katz, who also represents plaintiffs in drug and device litigation, said it’s too soon to tell how helpful the new requirements will be. “More transparency is always better than less, but I just don’t know if this is it. The proof will be in the pudding,” said Katz, of Englewood, Colo.

Katz noted that adverse event information is already supposed to be posted on the FDA’s website, but the data could be prone to manipulation. “You could have a few people that have the same adverse event, but two different reporters could characterize them differently. For example, there are six ways to describe a pulmonary embolism,” he said. “I’m sure there is a way for big pharma to comply without giving too much information, while other companies will follow the rules to the letter.”